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Trial record 4 of 6 for:    Immunocore

Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

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ClinicalTrials.gov Identifier: NCT03070392
Recruitment Status : Recruiting
First Posted : March 3, 2017
Last Update Posted : September 18, 2018
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Brief Summary:
To evaluate the overall survival of HLA-A*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.

Condition or disease Intervention/treatment Phase
Uveal Melanoma Biological: IMCgp100 Drug: Dacarbazine Biological: Ipilimumab Biological: Pembrolizumab Phase 2

Detailed Description:
This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A*0201 positive adult patients with advanced UM treated in the first line setting with no prior systemic or liver-directed chemo-, radio- or immune-therapy administered in the advanced setting (prior surgical resection of liver metastases and adjuvant systemic therapy are acceptable). Comparison of the IMCgp100 efficacy results in this Phase II study will be made with the concurrently randomized arm (Investigator's Choice) with a primary endpoint of overall survival (OS) and secondary efficacy endpoints of progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and disease control rate (DCR).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 327 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared With Investigator Choice in HLA-A*0201 Positive Patients With Previously Untreated Advanced Uveal Melanoma
Actual Study Start Date : October 16, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
Experimental: IMCgp100
Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)
Biological: IMCgp100
IMCgp100 is to be administered at 20 mcg cycle 1 day1, then 30 mcg cycle 1 day 8, then 68 mcg cycle 1 day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity

Active Comparator: Investigator's Choice

1 of 3 Investigator's Choice options: Systemic Dacarbazine

1 of 3 Investigator's Choice options: Systemic Ipilimumab

1 of 3 Investigator's Choice options: Systemic Pembrolizumab

Drug: Dacarbazine
Dacarbazine is to be administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity
Other Names:
  • DTIC-Dome
  • DTIC
  • DIC
  • Imidazole Carboxamide

Biological: Ipilimumab
Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments
Other Name: Yervoy

Biological: Pembrolizumab
Pembrolizumab is to be administered at 2 mg/kg IV infusion over 30 minutes every 3 weeks until confirmed disease progression or unacceptable toxicity
Other Name: Keytruda




Primary Outcome Measures :
  1. Overall survival defined as the time from patient inclusion to date of death due to any cause [ Time Frame: Survival status will be assessed every 3 months from randomization until death, assessed up to 40 months. ]

Secondary Outcome Measures :
  1. Safety defined as the number of patients with treatment emergent adverse events, laboratory abnormalities, ECG changes, and/or physical examination findings [ Time Frame: Safety will be assessed from informed consent through 90 days after end of treatment ]
  2. Efficacy: Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1) by Independent Central Review [ Time Frame: ORR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months ]
  3. Efficacy: Duration of response (DOR) defined as the time from first documented objective response (RECIST v1.1) by Independent Central Review until the date of documented disease progression [ Time Frame: DOR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months ]
  4. Efficacy: Progression free survival (PFS) defined as the time from randomization to the date of progression (RECIST v1.1) by Independent Central Review or death due to any cause [ Time Frame: PFS will be assessed every 3 months from randomization until disease progression or death, assessed up to 40 months ]
  5. Efficacy: Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1) by Independent Central Review. [ Time Frame: DCR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months ]
  6. Quality-of-Life: General health status will be assessed using the EQ-5D,5L questionnaire [ Time Frame: : EQ-5D,5L will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until death, assessed up to 40 months ]
  7. Quality-of-Life: Health related quality of life will be assessed using EORTC QLQ-C30 questionnaire [ Time Frame: EORTC QLQ-C30 will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until disease progression, assessed up to 40 months ]
  8. Pharmacokinetics (IMCgp100 Arm only): Area under the plasma concentration-time curve (AUC) [ Time Frame: AUC will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months ]
  9. Pharmacokinetics (IMCgp100 Arm only): The maximum observed plasma drug concentration after single dose administration (Cmax) [ Time Frame: Cmax will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months ]
  10. Pharmacokinetics (IMCgp100 Arm only): The time to reach maximum plasma concentration (Tmax) [ Time Frame: Tmax will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks ]
  11. Pharmacokinetics (IMCgp100 Arm only): The elimination half-life (t1/2) [ Time Frame: t1/2 will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks ]
  12. Pharmacokinetics (IMCgp100 Arm only): To assess the frequency of anti-IMCgp100 antibody formation [ Time Frame: Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 40 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients age ≥ 18 years of age at the time of informed consent
  2. Ability to provide and understand written informed consent prior to any study procedures
  3. Histologically or cytologically confirmed metastatic UM
  4. No prior systemic therapy in the metastatic or advanced setting
  5. No prior local, liver-directed therapy; prior surgical resection of oligometastatic liver disease is allowed
  6. Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in patients with localized disease

Exclusion Criteria:

  1. Impaired baseline organ function as evaluated by out-of-range laboratory values
  2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
  3. Clinically significant cardiac disease or impaired cardiac function
  4. Presence of symptomatic or untreated central nervous system (CNS) metastases
  5. Active infection requiring systemic antibiotic therapy
  6. Known history of human immunodeficiency virus infection (HIV)
  7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  8. Malignant disease, other than that being treated in this study
  9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive medication. Local steroid therapies are acceptable
  10. History of adrenal insufficiency, pneumonitis, interstitial lung disease, or inflammatory bowel disease
  11. Major surgery within 2 weeks of the first dose of study drug
  12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field
  13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug
  14. Pregnant, likely to become pregnant, or lactating women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070392


Contacts
Contact: Rachael Easton, MD, PhD 484-534-5261 rachael.easton@immunocore.com
Contact: Katie Blatt 484-534-5261 Katie.Blatt@immunocore.com

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Sponsors and Collaborators
Immunocore Ltd

Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT03070392     History of Changes
Other Study ID Numbers: IMCgp100-202
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Immunocore Ltd:
Melanoma
Uveal Cancer
IMCgp100
Immunotherapy

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Pembrolizumab
Antineoplastic Agents